1. Journal Club 2016年6月30日 8:30-8:55 ８階 医局 埼玉医科大学 総合医療センター 内分泌・糖尿病内科
Käyser SC, Dekkers T, Groenewoud HJ, van der Wilt GJ, Carel Bakx J, van der Wel MC, Hermus AR, Lenders JW, Deinum J.
Study Heterogeneity and Estimation of Prevalence of Primary Aldosteronism: a Systematic Review and Meta-regression Analysis.
J Clin Endocrinol Metab May 12:jc [Epub ahead of print]
Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr.
The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.
J Clin Endocrinol Metab May;101(5): doi: /jc Epub 2016 Mar 2.
2016年6月30日　8:30-8:55
８階　医局
埼玉医科大学　総合医療センター　内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
松田　昌文　
Matsuda, Masafumi

2. J Clin Endocrinol Metab. 2016 May 12:jc20161472.

3. Context: For health care planning and allocation of resources realistic estimation of the prevalence of primary aldosteronism is necessary. Reported prevalences of primary aldosteronism are highly variable, possibly due to study heterogeneity.
Objective: To identify and explain heterogeneity in studies that aimed to establish the prevalence of primary aldosteronism in hypertensive patients.

4. Data Sources: PubMed, EMBASE, Web of Science, Cochrane Library, and reference lists from 1–1–1990 to 31–1–2015.
Study Selection: Description of an adult hypertensive patient population with confirmed diagnosis of primary aldosteronism.
Data Extraction: Dual extraction and quality assessment.

5. Figure 1. Flow Diagram of Studies Considered for Systematic Review
Figure 1. Flow Diagram of Studies Considered for Systematic Review *The 36 articles contain 39 studies (patient cohorts). Mulatero, 2004 (20) and Rossi, 1998 (21) report 5 respectively 3 cohorts of which 4 respectively 1 were included. The reason for exclusion for exclusion of the cohorts are explained in Supplemental Table 1. As a result 36 (included articles) 60 (excluded articles) 94.

6. Table 1. Summary of Studies on Prevalence of Primary Aldosteronism in Primary Care and Referral Centers

7. Abbreviations: aldo, aldosterone; ARR, Aldosterone to Renin Ratio; Cross, Cross-sectional; FST, Fludrocortisone Suppression Test; HT, Hypertension; IV SLT, Intravenous Sodium Loading Test; n, number of patients; NR, Not Reported; Oral SLT, Oral Sodium Loading Test; PAC, Plasma Aldosterone Concentration; PC, Primary Care; PRA, Plasma Renin Activity; Prosp, Prospective; RC, Referral Center; ref, reference; Retro, Retrospective; RHT, Resistant Hypertension; SAC, Serum Aldosterone Concentration.
a Additional data received from author.
b Study design: partly retrospective.
c In this review, only patients who were assessed by our pre-defined inclusion criteria were included in the analysis (prevalence is 41/464 =8.8%). However, usually when cited, a prevalence of 9.2% is reported (56).
d Due to missing number of included patients, the study from Australia (Brisbane) is excluded.
e ARR ≥ 40 and/or post-captopril ARR ≥ 30 and/or LDH-score ≥ 0.50.
f ARR ≥ 40 plus post-captopril ARR ≥ 30 and/or LDH-score ≥ 0.50.
g Patients who were analyzed because of an incidentaloma were excluded.
h Patients studied in primary care were excluded due to < 50% confirmation test.

9. Figure 3. Abbreviations: GRA, Glucocorticold Remediable Aldosteronism; PA, Primary Aldosteronism.

10. from 3.2 to 12.7% in primary care and
from 1 to 29.8% in referral centers

12. Data Synthesis: 39 studies provided data on patients (9 studies, 5896 patients, from primary care). Prevalence estimates varied from 3.2 to 12.7% in primary care and from 1 to 29.8% in referral centers. Heterogeneity was too high to establish point estimates (I2 = 57.6% in primary care and 97.1% in referral centers). Meta-regression analysis showed higher prevalences in studies 1. published after 2000; 2. from Australia; 3. aimed at assessing prevalence of secondary hypertension; 4. that were retrospective; 5. that selected consecutive patients; 6. not using a screening test. All studies had minor or major flaws.

13. Conclusions: This study demonstrates that it is pointless to claim low or high prevalence of primary aldosteronism based on published reports. Because of the significant impact of a diagnosis of primary aldosteronism on health care resources and the necessary facilities, our findings urge for a prevalence study whose design takes into account the factors identified in the meta-regression analysis.

14. Message
原発性アルドステロン症の頻度：__%　？

17. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10. 1210/jc

18. Objective: To develop clinical practice guidelines for the management of patients with primary aldosteronism.

19. Participants: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee of the Endocrine Society, six additional experts, a methodologist, and a medical writer. The guideline was cosponsored by American Heart Association, American Association of Endocrine Surgeons, European Society of Endocrinology, European Society of Hypertension, International Association of Endocrine Surgeons, International Society of Endocrinology, International Society of Hypertension, Japan Endocrine Society, and The Japanese Society of Hypertension. The Task Force received no corporate funding or remuneration.
Evidence: We searched for systematic reviews and primary studies to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation group criteria to describe both the quality of evidence and the strength of recommendations. We used “recommend” for strong recommendations and “suggest” for weak recommendations.

25. Table 4. Measurement of ARR: A Suggested Approach
A. Preparation: agenda
1. Attempt to correct hypokalemia. Measure plasma potassium in blood collected slowly with a syringe and needle
[preferably not a Vacutainer to minimize the risk of spuriously raising potassium]. During collection, avoid fist
clenching, wait at least 5 seconds after tourniquet release (if used) to achieve insertion of needle, and ensure
separation of plasma from cells within 30 minutes of collection. A plasma [K] of 4.0 mmol/L is the aim of
supplementation.
2. Encourage patient to liberalize (rather than restrict) sodium intake.
3. Withdraw agents that markedly affect the ARR (219) for at least 4 weeks:
a. Spironolactone, eplerenone, amiloride, and triamterene
b. Potassium-wasting diuretics
c. Products derived from licorice root (eg, confectionary licorice, chewing tobacco)
4. If the results of ARR after discontinuation of the above agents are not diagnostic, and if hypertension can be controlled
with relatively noninterfering medications (see Table 5), withdraw other medications that may affect the ARR (219) for
at least 2 weeks, such as:
a. -Adrenergic blockers, central -2 agonists (eg, clonidine, -methyldopa), and nonsteroidal anti-inflammatory drugs
b. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and dihydropyridine
calcium channel antagonists
5. If necessary to maintain hypertension control, commence other antihypertensive medications that have lesser effects on
the ARR (e.g. verapamil slow-release, hydralazine [with verapamil slow-release, to avoid reflex tachycardia], prazosin,
doxazosin, terazosin; see Table 5).
6. Establish OC and HRT status because estrogen-containing medications may lower DRC and cause false-positive ARR
when DRC (rather than PRA) is measured (220). Do not withdraw OC unless confident of alternative effective
contraception.
B. Conditions for blood collection
1. Collect blood midmorning, after the patient has been up (sitting, standing, or walking) for at least 2 hours and seated
for 5–15 minutes.
2. Collect blood carefully, avoiding stasis and hemolysis (see A.1 above).
3. Maintain sample at room temperature (and not on ice, as this will promote conversion of inactive to active renin)
during delivery to laboratory and prior to centrifugation and rapid freezing of plasma component pending assay.
C. Factors to take into account when interpreting results (see Table 3)
1. Age: in patients aged 65 years, renin can be lowered more than aldosterone by age alone, leading to raised ARR.
2. Gender: premenstrual, ovulating females have higher ARR levels than age-matched men, especially during the luteal
phase of the menstrual cycle, during which false positives can occur, but only if renin is measured as DRC and not as
PRA (220).
3. Time of day, recent diet, posture, and length of time in that posture
4. Medications
5. Method of blood collection, including any difficulty doing so
6. Level of potassium
7. Level of creatinine (renal failure can lead to false-positive ARR)
Abbreviations: OC, oral contraceptives; HRT, hormone replacement therapy. [Adapted from J. W. Funder et al: Case detection, diagnosis, and treatment of patients with primary aldosteronism: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:3266–3281 (3), with permission. © Endocrine Society.]

29. What is new?
• Broadened indications for screening, to include subjects with sustained BP elevation above 150 mm Hg (systolic) and/or 100 mm Hg (diastolic).
• Recognition that stringent cutoffs for ARR and PAC produce a positive rate of approximately 5% of hypertensives with PA as so defined, most of whom have a unilateral APA; less stringent cutoffs give a positive rate of 10%, with the majority having IAH as the source of autonomous aldosterone secretion.
• Details of recent findings establishing somatic mutations as (currently) the explanation of aldosterone hypersecretion in approximately 50% of APA, and of similar germline mutations in FH-III.
• Strengthening the case for timely diagnosis and treatment of PA, based on mounting evidence for cardiovascular and renal damage.
• Explicit recommendations for referral by primary care physicians of patients with suspected PA to specialized centers for further work-up.
• Explicit suggestions for an abbreviated work-up in patients with spontaneous hypokalemia, renin levels below the detection limit plus florid hyperaldosteronism.
• Enhanced communication among and between care providers to optimize outcomes for patients with confirmed PA.
• Recognition that capacity constraints mean that most patients with PA will be unable to be screened in the foreseeable future, and that given the heightened risk profile of PA and its frequency in hypertension, occult PA constitutes a major public health issue.

30. Consensus Process: We achieved consensus by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple communications. With the help of a medical writer, the Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and Council successfully reviewed the drafts prepared by the Task Force. We placed the version approved by the Clinical Guidelines Subcommittee and Clinical Affairs Core Committee on the Endocrine Society's website for comments by members. At each stage of review, the Task Force received written comments and incorporated necessary changes.

31. Conclusions: For high-risk groups of hypertensive patients and those with hypokalemia, we recommend case detection of primary aldosteronism by determining the aldosterone-renin ratio under standard conditions and recommend that a commonly used confirmatory test should confirm/exclude the condition. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend that an experienced radiologist should establish/exclude unilateral primary aldosteronism using bilateral adrenal venous sampling, and if confirmed, this should optimally be treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia or those unsuitable for surgery should be treated primarily with a mineralocorticoid receptor antagonist.

32. Message 次の基準に1つでも合致すれば、原発性アルドステロン のスクリーニングを行う：
異なる日に測定した3回の血圧値がいずれも150/100 ㎜Hg超
既存の3剤併用療法に治療抵抗性を示す高血圧
4剤以上の併用療法で高血圧を管理中
高血圧で、血中カリウム低値
高血圧で、副腎偶発腫がある
高血圧と睡眠時無呼吸を合併している
高血圧で、家族に早発高血圧または40歳前の脳卒中 発症歴を持つ人がいる
第一度近親者全員が原発性アルドステロン症に伴う 高血圧を発症している